Current and future opportunities of autodissemination of pyriproxyfen approach for malaria vector control in urban and rural Africa

Despite the progress made in reducing malaria burden, new ways to address the increasing challenges of insecticide resistance and the invasion and spread of exotic malaria vectors such as Anopheles stephensi in Africa are urgently needed. While African countries are adopting larviciding as a complementary intervention for malaria vector control, the autodissemination technology has the potential to overcome barriers associated with the identification and treatment of prolific habitats that impede conventional larviciding approaches in rural settings. The autodissemination technology as a “lure and release” strategy works by exploiting the resting behavior of gravid mosquitoes to transfer lethal concentration of biological or chemical insecticide such as pyriproxyfen (PPF), an insect growth regulator (IGRs) to their oviposition sites and result in adult emergence inhibition. Despite the evidence of the autodissemination approach to control other mosquito-borne diseases, there is growing and promising evidence for its use in controlling malaria vectors in Africa, which highlights the momentous research that needs to be sustained. This article reviews the evidence for efficacy of the autodissemination approach using PPF and discusses its potential as efficient and affordable complementary malaria vector control intervention in Africa. In the previous studies that were done in controlled semi-field environments, autodissemination with PPF demonstrated its potential in reducing densities of captive population of malaria vectors such as Anopheles gambiae and Anopheles arabiensis. Of importance, empirical evidence and biology-informed mathematical models to demonstrate the utility of the autodissemination approach to control wild populations of malaria vectors under field environment either alone or in combination with other tools are underway. Among others, the key determining factors for future introduction of this approach at scale is having scalable autodissemination devices, optimized PPF formulations, assess its integration/complementarity to existing conventional larviciding, and community perception and acceptance of the autodissemination approach.

Despite the evidence of the autodissemination approach to control other mosquito-borne diseases, there is growing and promising evidence for its use in controlling malaria vectors in Africa, which highlights the momentous research that needs to be sustained.This article reviews the evidence for efficacy of the autodissemination approach using PPF and discusses its potential as efficient and affordable complementary malaria vector control intervention in Africa.In the previous studies that were done in controlled semi-field environments, autodissemination with PPF demonstrated its potential in reducing densities of captive population of malaria vectors such as
Any reports and responses or comments on the article can be found at the end of the article.

Introduction
Wide coverage and use of control interventions such as Insecticide treated bed nets (ITNs) and indoor residual spraying (IRS) have accelerated the gains in malaria burden reduction 1,2 .These core interventions are threatened by increasing insecticide resistance development mainly to pyrethroid class in targeted mosquito species 3,4 , shift to mosquitoes biting behavior to earlier hours of the evening and morning [5][6][7] , and outdoor mosquito biting when people aren't protected 8 .
To sustain these gains, WHO recommended larval source management (LSM) as a supplementary intervention to the core interventions 9 .LSM, particularly larviciding, has proved to be the potential in accelerating vector density reduction in areas where mosquitoes' breeding habitats are few, fixed, and findable 10 .Larviciding as an ecological method can reduce densities of both endophilic and exophilic vector populations 11 as well as malaria incidence and prevalence in selected settings 12,13 .Despite these notable progress and its historical success in malaria control, its wider application in rural African settings to cover productive cryptic breeding habitats requires different innovative strategies for its deployment 14 .
The major malaria vectors in Sub Saharan Africa are An.gambiae, An. arabiensis, Anopheles coluzzii and Anopheles funestus 15 .Studies have shown that the majority of residual malaria transmission is mainly mediated by An. funestus [16][17][18] and An.arabiensis 8,19 , which exhibit flexible behaviors including exophily 20 exophagy, and zoophagy 21,22 .Despite the efforts placed in controlling mosquitoes indoor, it is clear from the literature that ability of susceptible An. funestus and An.arabiensis to penetrate the bednets 23 , early indoor biting 7,24 , outdoor biting 25 as well as day biting 26 could evade the control efforts and sustain the transmission.Moreover, while continuing to deliver interventions that tackle indoor transmission, significant attention should be focused on mosquito behavior change, including outdoor biting and early indoor biting 7,8 .While investments in developing outdoor-based interventions are urgently required to sustain progress made on malaria control and elimination [27][28][29] , it is also important to consider the pertinent ecological and behavioral adaptations of the dominant malaria vectors 30 .
Promisingly, there has been an increase in designing and testing different outdoor mosquito control tools in recent years 31 .This includes the application of insecticides to alternative hosts such as livestock 21 ; assessing the potential use of large-scale spatial repellents 11,32,33 ; development of outdoors odor-baited traps 34 ; attractive targeted sugar baits 35 ; topical repellents 36 ; use of genetically modified mosquitoes 37 ; eave-ribbon technology 38 , as well as the autodissemination approach 39 .This review discusses the opportunities and challenges of autodissemination approach with pyriproxyfen for controlling malaria vectors in urban and rural Africa.

The autodissemination approach
Autodissemination approach is the management method that involves co-opting host seeking, ovipositing and resting adult female gravid mosquitoes' behavior to transfer a lethal concentration of chemical insecticide such as pyriproxyfen to the breeding habitats and consequently results to adult emergence inhibition 40,41 .Limited evidence suggests that adult Aedes albopictus male could directly deliver PPF to the breeding habitats or cross contaminate the females that will eventually deliver it to breeding habitat 42 .However, this strategy is likely to be hampered with mass rearing and release of male mosquitoes 42 .
The impetus for testing autodissemination approach for malaria vector control was inspired by Itoh and others who first showed that Aedes aegypti mosquitoes can be co-opted to autodisseminate insecticide 43 .Later on, in Peru, Devine and others convincingly demonstrated a 98% larval mortality and 42-98% adult emergence inhibition, with only 4% coverage of Aedes aegypti resting sites with pyriproxyfen 40 .Similar empirical benefits were also documented for Asian tiger mosquito, Aedes albopictus 41,44 .The successful demonstration of this novel mosquito assisted-larviciding approach in controlling non-malaria disease vectors has paved the way for investigating its utility for controlling malaria vectors.

The autodissemination technology for malaria control
Large semi-field cage studies have proven the efficacy of autodissemination with pyriproxyfen approach in controlling malaria vectors; An. gambiae 45 An. quadrimaculatus 46 and An.arabiensis 39 .These studies demonstrated that captive population of malaria vectors can successfully pick up the pyriproxyfen particles from contaminated surfaces and retain it until reaching a breeding habitat, where during the oviposition process, they contaminated the breeding habitat and render it unproductive.Using captive and stable self-sustaining populations of An. arabiensis, Lwetoijera and others demonstrated that only two clay pots that has been treated once with 10% active ingredient of pyriproxyfen were sufficient to crash the entire population within months of exposure 47 .This impact, that was recorded in a relatively small surface area of approximately 184 m 2 covered by 800 L of water in readily available breeding habitats is likely to have been delivered by a relatively small proportion of blood fed An. arabiensis that prefer to rest in clay pots 47 .Under expansive real-life settings, clay pots might compete with other nearby vegetations for resting mosquitoes.To that end, it becomes critical to ensure that purpose-built or contamination stations/devices treated with pyriproxyfen are highly attractive to visiting and resting mosquitoes, and the formulations used are efficacious and optimal to work in ultra-dosage.
There have been concerted efforts to generate highly optimized formulation of pyriproxyfen using microencapsulation technology.Previous analysis has demonstrated that microencapsulation is feasible for formulating insecticides for autodissemination and direct application into the aquatic habitats 48,49 .Some of the advantages offered by this innovative formulation include increased percentage of active ingredient (AI) within the formulation, thus reducing the number of mosquitoes that must be recruited to disseminate effective amounts of the formulation to the breeding habitats.In this way, microencapsulation has potential to increase formulation longevity in the field by protecting the AI from degradation by ultraviolet light, and reduce amount of insecticide and frequency of treating the autodissemination stations.
Moreover, electrostatic coating technology can be employed in the dissemination devices to increase the proportion of particles adhered to a mosquito's body 50 .The technology has already been used in pest control, for example in controlling sweet potato whitefly (Bemisia tabaci) 51 .In addition, electrostatic technology has been proved to increase the amount of insecticides particles taken by a single mosquito, enhancing bioavailability, and therefore a lower dose can be effective against mosquito consequently breaking resistance 50 .
Furthermore, numerous prototypes of autodissemination devices are being developed and tested for their efficacy in controlling vector population.Performance of a novel autodissemination station/device might depend on the attractiveness of the station to mosquitoes; pick-up rate of chemical by the mosquitoes as well as dissemination of picked chemicals to targeted breeding habitats 41 .It will also be worth considering device design with no/or minimal maintenance requirements, low cost and low risk to people who might come in contact with it 41 .Consideration has been made with regard to the mentioned factors for a good autodissemination device; for example the development of In2Care® trap 52 , and promising results from the assessment of its efficacy in controlling Aedes aegypti and Aedes albopticus population in both semi-field and field evaluation settings [53][54][55] .Most of the autodissemination devices have been designed and tested for mosquito species other than Anopheles species 56,57 .
With good performance in controlling Aedes mosquitoes, it's important to test the effectiveness of these available autodissemination devices in controlling malaria vectors.Lwetoijera and others used the clay pots as the autodissemination devices in semi-field settings for An.arabiensis 39 .Worryingly, the clay pots are fragile and impractical for large-scale deployment, but also faces competition from other resting sites in the field environment, which necessitate a new design that is more attractive to resting mosquitoes.
Owing to the paucity of breeding habitats during dry season, the application of autodissemination approach at this time point is likely to deliver desired impact [58][59][60] .Because mosquito abundance during dry season is low 59,61 , the effectiveness of autodissemination approach, items of delivering lethal dosage of pyriproxyfen to breeding habitats, is likely to be achieved via multiple visits of gravid mosquitoes to the breeding habitats during sequential egg laying cycles by targeted Anopheles species 62 .In addition, Culex mosquitoes that often share breeding habitats with Anopheles have potential to improve coverage of the target breeding habitats with pyriproxyfen 59,63 .
Despite high mosquito densities associated with rainy season, application of autodissemination is likely to be impractical due to plethora and expansive nature of the breeding habitats in which the lethal concentration of pyriproxyfen cannot be achieved 62,64 .Failure to achieve lethal concentrations at the habitats might amplify pyrethroid resistance in mosquito population exposed to sub-lethal dosage of pyriproxyfen 65 .Table 1 summarizes studies on use of autodissemination with different IGR for malaria vector control.

The autodissemination technology over conventional larviciding
Conventional larviciding with biological larvicides has worked best as a complementary malaria control intervention 60 .Implementation of the larviciding program in several sub-Saharan African countries has greatly reduced the malaria burden 12 .For effective larviciding, WHO recommends, application to be done in areas where larval habitats are fixed, few, and findable, often found in urban settings 9 .Hence, numerous breeding habitats that are often scattered and hard to locate have remained as major challenges for larviciding programs in peri-urban and rural settings 14,66 .Even with strong political will, effective community engagement and participation, some of these operational challenges might not be fully addressed.
As solution options, the use of unmanned aerial vehicles (UAVs) to identify breeding habitats for larviciding at wider scales is increasingly proposed 67-69 .However, long processing time and technical skills required to operate UAV and handle generated data, and the need to map all the targeted breeding habitats may hamper the scale-up of this approach 68,70 .
Alternatively, autodissemination with pyriproxyfen has the potential to complement conventional larviciding through coverage amplification of cryptic, myriad and hard to reach breeding habitats 71,72 .As promising as it may sound, significant and cost-effective contribution of combining the two approaches, its impact on entomological and epidemiological disease outcomes highlights the gaps that needs to be explored.

Pyriproxyfen as the biorational pesticides for autodissemination approach
Pyriproxyfen is a juvenile hormone analog, that interferes with the metamorphosis of mosquitoes and therefore prevents adult emergence 73 with an additional benefit of sterilizing female mosquitoes [74][75][76] .A miniscule PPF amount of 50 ppb has been approved for mosquito control.This amount is six times below the maximum recommended limit of 300 ppb in drinking water 77 .Among other factors, low mammalian toxicity, safety to aquatic organisms 78,79 and a long-term persistency up to 6 months in the field breeding habitats 80 , makes the use of PPF in larviciding programs advantageous.
Pyrethroid resistance to malaria vectors has been reported to be mostly of metabolic origin 3,4 .Despite that PPF is being metabolized in a same way as pyrethroids 81,82 , and no evidence of resistance development in malaria vectors against PPF has been documented 83 .However, there is a need to closely monitor resistance of this novel larvicide 82 .

Potential integration to current malaria interventions
Autodissemination (mosquito-assisted larviciding) has the potential to complement the existing frontline malaria interventions in rural and urban settings.LLINs and IRS have contributed nearly 40% of the 57% reduction in incidence of clinical diseases, representing over 81% relative contribution to the success in malaria control for the past two decades 1 and 23% reduction in child mortality across most endemic sub-Saharan countries 84 .These assuring progresses has further fueled the development of next generation LLINs and chemistries for IRS to ensure its usefulness against resistant mosquito populations [85][86][87] .
The use of autodissemination with pyriproxyfen has potential to complement these tools by controlling mosquitoes at its breeding habitats.Convincingly, the use of pyriproxyfen via conventional larviciding has already demonstrated effectiveness in preventing emergence of An. arabiensis and An.funestus at experimental scale in the field settings 88,89 .Pyriproxyfen can also sterilize adult malaria vectors through contact with treated nets, such as Olyset Duo nets [90][91][92] , offering a promising opportunity to control insecticide resistant mosquitoes 92,93 .
Of importance, it has been demonstrated that sterilized mosquitoes can still transfer PPF sufficient to prevent adult emergence at the contaminated habitats 94 .This development, highlights the unique complementarity of autodissemination with bednets co-treated with pyriproxyfen.At population level, mosquito will be sterilized following exposure to LLINs treated with PPF, and inhibited from emerging at breeding habitats.
A semi field-study by Swale and others demonstrated that An. quadrimaculatus can deliver a sufficient novaluron, a chitin synthesis inhibitor, to its breeding habitats via autodissemination approach and cause adult emergence inhibition 46 .Until recent, major malaria vectors An. arabiensis, An. gambiae and An.funestus under semi-field settings have proven to be susceptible to novaluron 95 .Furthermore, it is extremely important that future research should look at the possibility to other explore alternative IGRs that could be used for autodissemination approach in rotation with pyriproxyfen.Habitat-based modelling by Gu and Novak highlighted that in order to combat malaria in Africa, larval interventions should be focused in identifying and targeting prolific habitats 96 , a task that might be accomplished with near perfection using autodissemination approach, based on the evidence that gravid mosquitoes know better their most preferred habitats 71,72 .Hence, it is our expectation that eventual deployment of autodissemination with pyriproxyfen might further accelerate these control efforts by amplifying the coverage of pyriproxyfen to the productive breeding habitats.While studies to demonstrate the entomological impact of autodissemination with pyriproxyfen under field settings where LLINs are widely used are ongoing, future trials should also aim to establish the combined impact of autodissemination and LLINs and/or other interventions to understand whether the overall effect would be synergistic, additive, or antagonistic.
Autodissemination technology itself as a novel vector control tool, can be integrated with other malaria intervention in a cost-effective way.Autodissemination with PPF can contribute to tools box for controlling Anopheles stephensi in urban settings.Since its first report in Djibouti 97 , An. stephensi has spread to Ethiopia, Somalia and Sudan and Nigeria 2 and more recently in Kenya (E.Ochomo, unpublished report).Similar to Aedes mosquitoes, An. stephensi mostly breed in man-made water storage containers and discarded wastes 98 .Successful establishment of this species in urban settings, where discarded wastes are ubiquitous and poorly managed, will pose great challenge to malaria control efforts.The geo-statistical model predicted the "worst case scenario" where by more than 126 million people residing in African cities will be at risk of contracting malaria if no action is taken 99 .Scientists have argued that, instead of addressing the threat as stand alone, it's important to use integrated response that can also target other malaria vectors, and hence proper utilization of resources to fit different contexts 100 .Similar to the successes made in controlling Aedes mosquitoes using autodissemination with pyriproxyfen elsewhere 101 , this approach is well suited and can be effectively integrated into conventional larviciding programs to specifically target breeding habitats of An. stephensi.This approach might be more applicable and cost-effective in urban settings with low transmission and where widespread use of LLINs is unjustified 102 .
Impact of community involvement in malaria control should never be underrated.Strong collaboration amongst different experts, including affected communities, is necessary for effective malaria control 103 .The sensitive role of the community in mosquito control is well documented 104,105 .Similar to other malaria interventions, scaling up autodissemination technology shall strongly need community participation, to get the desired impact.However, the evidence of engaging communities with regards to PPF-based studies is limited and therefore needs to be explored 106 .
Because the autodissemination stations will be placed outside near human dwellings, raising awareness to the community on the safety of PPF to humans especially children that might come into contact with the stations is critical.Contamination of the environments, including human and animal drinking water with PPF deposited by contaminated mosquitoes, will also necessitate community involvement, approval and ownership of the autodissemination approach in their locality.
The autodissemination technology will be deployed in parallel with environmental cleaning that will not only reduce vegetations exploited by resting mosquitoes, but also maximize mosquito resting time in the provided autodissemination stations.For this reason, it will be important to encourage and empower communities with trainings on household environmental cleaning that will directly reduce mosquito densities and associated bites 107 .

Conclusion
Evidences supporting the future use of autodissemination approach with pyriproxyfen for malaria control are increasingly documented but more studies on field validation of this approach to formulate its target product profile are required.Among factors that should be looked at include scalable autodissemination devices with potential to target wide range of Anopheles behavior such as mating, host-seeking, resting and Para 2 on the same page, the authors have commented that larval interventions should be focussed...a task that might be accomplished using autodissemination, please clarify how this will be achieved?○ Conclusion -line 5 -Among factors that should be looked at include scalable autodissemination devices...to target wide range of Anopheles behaviour -can the authors explain which behaviour they are referring to?

Typographical:
The article is well written, however, a few minor typographical corrections are needed.which are as under: Abstract: sentence three needs to be amended with the addition of word inhibition -The autodissemination technology as a lure and release...adult emergence [inhibition].

1.
Page 3, Introduction: subheading-"The autodissemination approach" -Please italicize Aedes albopictus.Please add ref to the statement that "Limited evidence suggests that adult Aedes albopictus males could deliver..."
Page 4 second column second para -line 1 delete "of" after despite; delete "below" after Table 1.
Page 4 second column fourth para -line 5 "impact of" should be -"impact on".8.
Page 5 second column -line 5 instead of "contribute" it should be "contribution".9.
Page 6 para 2 -line 12 -it should be "highlights" instead of "highlight"; para 3 line 4 -it should be "near perfection" and not "nearly"; line 5 it should be "expectation" and not "expectations"; para 4 line 2 amend can be integrated with other instead of into other; same para line 16 -remove colon after "scientists have argued that".

10.
Page 6 second column first para -last line -add "use after widespread"; second para rephrase second sentence to make it more clear -"Malaria control needs..." 11.

Are the conclusions drawn appropriate in the context of the current research literature? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Vector borne diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Dickson Wilson Lwetoijera
We thank the reviewer for their thoughtful and constructive comments on this manuscript.In the revised version, we have made the following changes and possible clarifications on technical queries and typographical suggestions as per the reviewers' comments.

Technical
Comment 1: The authors on page 6 para 2 have mentioned that larviciding with PPF and adult control through PPF-treated LLIN will complement each other.Will exposure at both stages not enhance the development of resistance especially given the fact that pyrethroid resistance will be affected?Please clarify.

Response:
At the population level, mosquitoes will be sterilized following exposure to LLINs treated with PPF and will be inhibited from emerging in breeding habitats.To date, there is limited evidence on the effect of PPF on pyrethroid resistance; a previous study exploring the effect of sub-lethal PPF doses on pyrethroid resistance in Anopheles arabiensis was only performed for a single generation, which makes it unclear whether the observable magnification of pyrethroid resistance is just tolerance or actual resistance that can be inherited over multiple generations.
Comment 2: Tilak: Para 2 on the same page, the authors have commented that larval interventions should be focussed a task that might be accomplished using autodissemination, please clarify how this will be achieved?.
Response: A task that might be accomplished with near perfection using autodissemination approach, based on the evidence that gravid mosquitoes know better their most preferred habitats Comment 3: Conclusion -line 5 -Among factors that should be looked at include scalable autodissemination devices...to target wide range of Anopheles behaviour -can the authors explain which behaviour they are referring to?
Response: In the line 5 of conclusion section, the Anopheles behaviors that the authors referred to were mating, host-seeking, resting, and oviposition.

Typographical
Comment 1: Abstract: sentence three needs to be amended with the addition of word inhibition -The autodissemination technology as a lure and release...adult emergence [inhibition].

Response:
The word "inhibition" has been added in sentence three of the abstract, which now reads "The autodissemination technology as a "lure and release" strategy works by exploiting the resting behavior of gravid mosquitoes to transfer lethal concentration of biological or chemical insecticide such as pyriproxyfen (PPF), an insect growth regulator (IGRs) to their oviposition sites and result in adult emergence inhibition".
Comment 2: Page 3, Introduction: subheading-"The autodissemination approach" -Please italicize Aedes albopictus.Please add ref to the statement that "Limited evidence suggests that adult Aedes albopictus males could deliver..."

Response:
The Species name Aedes albopictus has been italicized.Also, the article by Mains et al., 2015 has been added as a reference for the sentence that reads "Limited evidence suggests that adult Aedes albopictus male could directly deliver PPF to the breeding habitats or cross contaminate the females that will eventually deliver it to breeding habitat (Mains et  al., 2015).

Response:
The word "contamination" has been replaced with "contaminated" and "contaminated" replaced with "contaminate" in the introduction subheading section, page 3.
Comment 4: Page 4, para 4-last line design that is "more attractive" instead of "attractiveness".
Response: On page 4, para 4 -last line, the word "attractiveness" has been replaced with "attractive".Now the sentence reads "Worryingly, the clay pots are fragile and impractical for large-scale deployment but also face competition from other resting sites in the field environment, which necessitate a new design that is more attractive to resting mosquitoes.

Response:
The word "specie" has been replaced with "species".Also, the word "has" has been replaced with "have" in page 4 second column fist para -line 7 as suggested by the reviewer.
Comment 6: Page 4 second column second para -line 1 delete "of" after despite; delete "below" after Table 1.
Response: On page 4 second column second para -line 1, the words "of" and "below" have been deleted.
Comment 7: Page 4 second column third para -line 9 after "remained" delete "to be" and "add as".
Response: On page 4 second column third para -line 9, the words "to be" have been replaced with "as" Comment 8: Page 4 second column fourth para -line 5 "impact of" should be -"impact on".regulators (IGRs) has gained significant interest, demonstrating efficacy in controlling Aedes mosquitoes in various field and semi-field settings.However, limited information exists regarding its effectiveness against Anopheline mosquitoes.This review presents updated information on the autodissemination of pyriproxyfen approach for malaria vector control in urban and rural Africa.The authors emphasize the importance of key factors such as the development of scalable autodissemination devices, optimized PPF formulations, assessment of integration with existing conventional larviciding methods, and community perception and acceptance of the autodissemination approach for successful implementation at a larger scale.The manuscript is well written, statements are referenced as required and appropriate conclusion provided.
Additionally, there is a study by Okazawa et al. (1991) 1 that demonstrates the efficacy of PPF in inhibiting adult emergence of Anopheles punctulatus.

2.
It would be worthwhile to investigate the presence of evidence supporting the effectiveness of PPF in controlling insecticide-resistant mosquitoes.

3.
Considering the reported ineffectiveness of PPF for An.quadrimaculatus (Swale et   This manuscript provides an overview of the current evidence of the potential role of autodissemination for malaria vector control including experiments conducted in the laboratory and large semi-field systems.Importantly, the authors have identified the factors that need to be addressed for successful implementation of the auto-dissemination strategy for control of malaria vectors.The manuscript identifies the need to conduct additional studies to increase the evidence on possible role of auto-dissemination strategy as an effective complementary tool for malaria vector control.The manuscript is well written, statements are referenced as required and appropriate conclusion provided. Minor issues Page 3 (the sub-title "The autodissemination approach") -Can male Anopheles also be targeted for transfer of pyriproxyfen?Probably discuss this in this section of the manuscript.See the article Mains et al., (2015) 1 .

2.
Add the article by "Swale et al., 2018 Development of an autodissemination strategy for the deployment of novel control agents targeting the common malaria mosquito, Anopheles quadrimaculatus say (Diptera: Culicidae)" 2 to Table 1 on the list of studies on autodissemination technology with different insect growth regulators (IGR) for controlling different malaria vectors.

3.
Page 4 -Is the difficulty to identify/develop more attractive oviposition-based traps/dissemination stations another limitation in the use of auto-dissemination approach in the control of malaria vectors? 4.

Oscar Mbare 1 1 Reviewer
International Centre of Insect Physiology and Ecology, Nairobi, Kenya 2 International Centre of Insect Physiology and Ecology, Nairobi, Kenya Accept Is the topic of the review discussed comprehensively in the context of the current literature?Yes Are all factual statements correct and adequately supported by citations?Yes Is the review written in accessible language?Yes Are the conclusions drawn appropriate in the context of the current research literature?Yes Competing Interests: No competing interests were disclosed.Reviewer Expertise: Malaria ecology, vector biology and vector control I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.Version Report 03 April 2023 https://doi.org/10.21956/wellcomeopenres.21208.r55603© 2023 Mbare O.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Oscar Mbare 1 International Centre of Insect Physiology and Ecology, Nairobi, Kenya 2 International Centre of Insect and Ecology, Nairobi, Kenya 3 International Centre of Insect Physiology and Ecology, Nairobi, Kenya

Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature?
al. 2018), it would be valuable to explore alternative IGRs as potential options for controlling insecticide-resistant mosquitoes.Yes settings have proven to be susceptible to novaluron(Ngonzi et al., 2022).Furthermore, it is extremely important that future research should look at the possibility to other explore alternative IGRs that could be used for autodissemination approach in rotation with pyriproxyfen.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.